POS0051 DRUG RETENTION AND REASONS FOR DISCONTINUATION OF BIOLOGICS AND JAK INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS – THE ANSWER COHORT STUDY
Authors: K. Ebina, Y. Etani, Y. Maeda, Y. Okita, M. Hirao, W. Yamamoto, M. Hashimoto, K. Murata, R. Hara, K. Nagai, Y. Hiramatsu, Y. Son, H. Amuro, T. Fujii, T. Okano, Y. Ueda, M. Katayama, T. Okano, A. Kumanogoh, S. Okada, K. Nakata
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> 2022 EULAR recommendation announced that both biological disease-modifying antirheumatic drugs (bDMARDs) and janus kinase inhibitors (JAKi) are considered in the phase Ⅱ treatment of rheumatoid arthritis (RA). However, we still lack reliable evidence of direct comparison between these agents' retention, which may reflect effectiveness and safety. <h3>Objectives</h3> The aim of this multi-center (7 university-related hospitals)<sup>[1]-[3]</sup>, retrospective study is to clarify the factors affecting treatment retention of bDMARDs and JAKi in a real-world setting. <h3>Methods</h3> This study assessed 6,666 treatment courses of bDMARDs and JAKi introduced from 2001 to 2022 (TNF inhibitors [TNFi]=3,577, anti-IL-6 receptor antibody [aIL-6R]=1,497, cytotoxic T lymphocyte-associated antigen-4-Ig [CTLA4-Ig]=1,139, JAKi=453; Bio/JAK naive cases 55.4%, baseline age 58.8 years, female 82.6%, disease duration 9.7 years, DAS28-ESR 4.3, concomitant methotrexate [MTX] [52.8%], other csDMARDs [26.0%], and oral glucocorticoid [GC] [36.4%]). Reasons for discontinuation were classified into four categories by each attending physician: 1) lack of effectiveness (primary and secondary), 2) toxic adverse events (infection, malignancies, and cardiovascular events, et al.), 3) non-toxic reasons (patient preference, change in hospital, and pregnancy, et al.), and 4) remission. Retention rates of each discontinuation reason were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, concomitant GC, MTX, and other csDMARDs, switched number of bDMARDs or JAKi, and prior use of TNFi, aIL-6R, CTLA4-Ig, or JAKi) using Cox proportional hazards modeling. <h3>Results</h3> Adjusted retention rates for each discontinuation reason were as follows: due to lack of effectiveness was aIL-6R=80.9%, JAKi=75.2%, CTLA4-Ig=73.6%, and TNFi=66.1% (Cox P&lt;0.001 between 4 groups) (figure 1a), due to toxic adverse events was CTLA4-Ig=88.0%, JAKi=86.4%, aIL-6R=84.1%, and TNFi=83.6% (Cox P=0.052) (figure 1b), due to non-toxic reasons was aIL-6R=86.9%, TNFi=85.9%, JAKi=85.9%, and CTLA4-Ig=82.6% (Cox P=0.064), and due to remission was JAKi=97.1%, CTLA4-Ig=96.7%, aIL-6R=96.0%, and TNFi=94.9% (Cox P=0.18). Compared to TNFi, aIL-6R (hazard ratio [HR]=0.54, 95%CI=0.47–0.61, P&lt;0.001), JAKi (HR=0.69, 95%CI=0.56–0.85, P&lt;0.001), and CTLA4-Ig (HR=0.75, 95%CI=0.66–0.86, P&lt;0.001) showed lower discontinuation rate due to lack of effectiveness. Compared to TNFi, CTLA4-Ig showed lower discontinuation rate due to toxic adverse events (HR=0.77, 95%CI=0.63–0.93, P=0.008) and remission (HR=0.67, 95%CI=0.46–0.98, P=0.041). Other factors increasing drug discontinuation due to lack of effectiveness was switched number of bDMARDs or JAKi (HR=1.42, 95%CI=1.24–1.63, P&lt;0.001), concomitant GC (HR=1.17, 95%CI=1.06–1.29, P=0.0018), and prior aIL-6R use (HR=1.24, 95%CI=1.05–1.45, P=0.011). On the other hand, higher age (HR=1.01, 95%CI=1.00–1.02, P&lt;0.001) and concomitant GC (HR=1.29, 95%CI=0.47–0.61, P&lt;0.001) increased drug discontinuation due to toxic adverse events. <h3>Conclusion</h3> Adjusted by potential confounders, aIL-6R showed lowest discontinuation due to lack of effectiveness, and CTLA4-Ig showed lowest discontinuation due to toxic adverse events. Besides the difference of bDMARDs and JAKi, concomitant GC increased drug discontinuation due to lack of effectiveness and toxic adverse events. <h3>References</h3> [1]Ebina K, et al. Drug tolerability and reasons for discontinuation of seven biologics in 4466 treatment courses of rheumatoid arthritis-the ANSWER cohort study. Arthritis Res Ther. Apr 11 2019;21(1):91. [2]Ebina K, et al. Drug retention of 7 biologics and tofacitinib in biologics-naive and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study. Arthritis Res Ther. Jun 15 2020;22(1):142. [3]Ebina K, et al. Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study. Sci Rep. Jan 7 2022;12(1):134. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Kosuke Ebina Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho, and UCB Japan., Consultant of: Asahi-Kasei and Taisho., Grant/research support from: AbbVie, Asahi-Kasei, Eisai, Mitsubishi-Tanabe, and Teijin Pharma. Affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho., Yuki Etani Grant/research support from: Eli Lilly, Yuichi Maeda Speakers bureau: Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Pfizer Inc., Bristol Myers Squibb, and Mitsubishi Tanabe Pharma Corporation, Grant/research support from: Eli Lilly, Yasutaka Okita Speakers bureau: Chugai Pharmaceutical, Pfizer, and Ono, Makoto Hirao Speakers bureau: Astellas, Ono Pharmaceutical, Eli Lilly, Mitsubishi-Tanabe, Pfizer, Ayumi, and Takeda, Wataru Yamamoto: None declared, Motomu Hashimoto Speakers bureau: Mitsubishi-Tanabe, Eisai, Eli Lilly, Bristol-Myers Squibb, and Novartis Pharma, Grant/research support from: Mitsubishi-Tanabe, Eisai, Eli Lilly, Bristol-Myers Squibb, and Novartis Pharma, Koichi Murata Speakers bureau: AbbVie GK, Eisai Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Bristol-Myers Squibb, Daiichi Sankyo Co. Ltd., and Asahi Kasei Pharma Corp., Grant/research support from: Daiichi Sankyo, Ryota Hara Speakers bureau: AbbVie and Eisai, Koji Nagai: None declared, Yuri Hiramatsu: None declared, Yonsu Son: None declared, Hideki Amuro: None declared, Takayuki Fujii Speakers bureau: Asahi Kasei Pharma, Abbvie, Jansen, Tanabe Mitsubishi Pharma, and Eisai, Takaichi Okano: None declared, Yo Ueda: None declared, Masaki Katayama: None declared, Tadashi Okano Speakers bureau: Abbvie, Chugai, Eli Lilly, Janssen and Novartis Pharma., Grant/research support from: Abbvie, Asahi Kasei, Chugai, Eisai, Eli Lilly and Tanabe Mitsubishi., Atsushi Kumanogoh Speakers bureau: Chugai, Eisai, Tanabe-Mitsubishi, Abbvie, and Ono, Grant/research support from: Chugai, Seiji Okada: None declared, Ken Nakata Grant/research support from: Astellas.